tbuckley/cabot-search huggingface dataset:
Opinions and usage of cancer-associated thrombosis scoring systems among hematologists and oncologists: An international survey.
Authors: Amulya Agrawal, Taha Bat, Ibrahim Ibrahim, Sung-Hee Choi, Adeel Khan
Journal: Journal of Clinical Oncology (2023)

e22531 Background: Cancer-associated thrombosis (CAT) occurs in 20% of cancer patients and is currently their second leading cause of death. Several scoring systems (i.e., Khorana Risk Score, COMPASS-CAT, Vienna-CATS, etc) have been developed to allow clinicians to determine CAT risk and prescribe appropriate treatments. There is little data about how hematologists and oncologists use these risk assessment models in daily practice. We conducted a survey of hematologists and oncologists in different institutions about their usage and opinions of CAT scoring systems. Methods: We created a twelve-question survey querying hematologists and oncologists regarding their usage and perspectives on CAT and scoring systems. Survey participation was voluntary, non-incentivized, and anonymous. The survey was advertised on social media and email list groups from January to February 2023. Descriptive statistics were analyzed in R version 4.1.2. Results: Seventy hematologists/oncologists responded with 88.4% from the US and 11.6% international. The plurality of respondents (35.7%) identified as sub-specialty oncologists (e.g., GI oncology, thoracic oncology, etc), 18.6% identified as malignant hematologists, and 15.7% identified as non-malignant hematologists. Overall 71.4% of respondents worked in academic settings. The majority (57.1%) stated they do not use any CAT scoring system and 15.7% stated they do not have familiarity with any CAT scoring system. Zero respondents strongly agreed that they often use scoring systems. Of the CAT systems used, the Khorana score was by far the most common (80.0%). Respondents somewhat agreed (14.3), somewhat disagreed (10%), or were undecided (34.3%) that scoring systems make it easier to determine CAT risk in practice. The majority (54.3%) were also undecided that these systems’ predictions of CAT risk are accurate. There was general agreement in worry of bleeding in anticoagulating cancer patients prophylactically (strongly agree 12.9%, agree 32.9%, somewhat agree 22.9%). Respondents strongly agreed (34.3%) or agreed (40.0%) that decisions about anticoagulation are important part in cancer patients’ supportive care. Similarly, respondents strongly agreed (30.0%), agreed (38.6%), or somewhat agreed (22.9%) that counseling patients on CAT is important. Conclusions: To our knowledge, this is the first survey assessment of hematologists and oncologists regarding their opions on CAT and their usage patterns of scoring systems. Despite the widespread agreement that counseling regarding CAT is important and that decisions about anticoagulation are a vital part of a cancer patient's supportive care, most clinicians do not use CAT scoring systems in practice or are not familiar with them. Hematologists and oncologists worry about the risk of bleeding with anticoagulation and agree there is a need for new and improved CAT scoring systems.
Trends, sociodemographic and hospital-level factors associated with inpatient palliative care utilization among malignant melanoma patients: A 5-year National Inpatient Sample (NIS) study.
Authors: Ayobami Gbenga Olafimihan, Inimfon Jackson, Jay Vakil, Philip Onyekaoso Kanemo, Rafaella Litvin, Khaldun Obeidat, Ekrem Turk, Muhammad Bilal Ibrahim, Rohan Gajjar, Kunnal Batra
Journal: Journal of Clinical Oncology (2023)

e21526 Background: Palliative care improves the quality of life in cancer patients; however, there is no literature on specific factors that predict its use in patients with malignant melanoma. We explored the prevalence trends, and predictors of palliative care utilization among hospitalized patients with malignant melanoma. Methods: Retrospective analyses were conducted using the National Inpatient Sample (NIS) data collected between 2016 and 2020. Descriptive analyses and multivariable regression models were used to investigate the prevalence trends, and sociodemographic and hospital-level factors associated with palliative care utilization in hospitalized malignant melanoma patients. Results: Of the 9,760 hospitalizations with a diagnosis of malignant melanoma over the study duration, 14% utilized palliative care during their hospital stay. Overall, 9.2% of malignant melanoma patients used palliative care and were discharged alive. There was a stable trend of palliative care use over the 5-year period (14%). Compared to patients on Medicare, those on Medicaid were twice (adjusted odds ratio (AOR): 2.12; 95% confidence interval (CI): 1.263.64) more likely to utilize palliative care. Relative to other regions in the US, patients hospitalized in the West were 40% less likely to receive the service of the palliative team (AOR: 0.61; 95% CI: 0.38-0.96). Those admitted to teaching hospitals (AOR: 0.55; 95% CI: 0.40-0.77) had lower odds of having palliative care consultations when compared to non-teaching hospitals. Patients admitted to urban hospitals had 50% (AOR: 0.51; 95% CI: 0.270.98) lesser odds of getting palliative care when compared to their counterparts in rural hospitals. Individuals who were either discharged to a facility/with home health (AOR: 8.81; 95% CI: 5.8813.23) or died during hospitalization (AOR: 128.42; 95% CI: 72.10228.77) had higher odds of utilizing palliative care when compared to those with a routine discharge. Conclusions: The prevalence of palliative care utilization was low, and factors associated with utilization in our population were identified. Our findings emphasize the necessity to improve awareness among medical oncologists and primary inpatient teams on the importance of involving the palliative care service early in the management of hospitalized patients with malignant melanoma.
A randomized phase 2 trial of encorafenib + binimetinib + nivolumab vs ipilimumab + nivolumab in BRAFV600-mutant melanoma brain metastases: SWOG S2000.
Authors: Zeynep Eroglu, James Moon, Yana G. Najjar, Rupesh Kotecha, Vadim Spektor, Michael Wu, Elad Sharon, Kenneth F. Grossmann, Jedd D. Wolchok, Sapna Pradyuman Patel, Hussein A. Tawbi
Journal: Journal of Clinical Oncology (2023)

TPS9603 Background: While anti-PD-1 and anti-CTLA4 immunotherapies are widely used in the treatment of metastatic melanoma, including melanoma brain metastases (MBM), their efficacy in patients with symptomatic MBM is very limited. In the Checkmate-204 trial of ipilimumab with nivolumab in MBM, the 6-month progression free survival (PFS) rate was 19% with a median PFS of only 1.2 months in symptomatic participants (those with neurological symptoms including steroids up to 4 mg/day of dexamethasone, n=18). (Tawbi, Lancet et al., 2021) In the COMBI-MB study of BRAF/MEK-inhibitors in BRAF-V600 mutant MBM, median PFS was 5.5 months in those with symptomatic metastases (n=17). (Davies et al., Lancet Oncol, 2017) The combination of anti-PD-1/PD-L1 therapy with BRAF/MEK inhibitors has been tested in various trials. The single-arm phase 2 TRICOTEL study explored the triplet regimen of vemurafenib + cobimetinib + atezolizumab in MBM; in the symptomatic brain met cohort, 6-month PFS was 57% (n=24). (Dummer et al., Lancet Oncol 2022). Methods: SWOG S2000 is a randomized phase 2 trial exploring the efficacy of a triplet regimen of BRAF/MEK inhibitors with PD-1 therapy (encorafenib 450 mg qday + binimetinib 30 mg BID + nivolumab 480 mg IV q4 weeks) versus ipilimumab 3 mg/kg + nivolumab 1 mg/kg q3 weeks in patients with symptomatic BRAF-mutant MBM. (The study was amended to exclude patients with asymptomatic MBM.) Eligible patients are ≥18 years old, ECOG 0-2, and prior neoadjuvant or adjuvant anti-PD-1, CTLA-4, or BRAF/MEK-inhibitors is permitted. Steroids up to 8 mg of dexamethasone/day (or equivalent), leptomeningeal spread, and prior local therapy (radiation or surgery) for brain mets are permitted, if a patient has at least one measurable, progressing brain met ≥0.5 cm in size. Primary objective is to compare PFS per (RECIST 1.1) between the two study arms. Secondary objectives include overall survival, toxicity profile, objective tumor response, intracranial response and duration per modified RECIST 1.1, modified RANO-BM, and iRANO criteria, and evaluation of radiographic response criteria by centralized review of banked images. This study is powered to detect an increase in estimated 6-month PFS from 20% to 52% with 80% power and type I error rate of 10%, with 24 eligible patients required. Total sample size is 28 to account for ineligible patients. Available blood, tissue, CSF and stool samples are banked for future correlative studies. The study is currently enrolling patients through SWOG, ECOG and NRG centers. Funding: NIH/NCI grants U10CA180888, U10CA180819, U10CA180820 U10CA180868; and in part by Pfizer, Inc. Clinical trial information: NCT04511013 .
Trabectedin failure-free survival (TFFS) after resuming trabectedin (T) in advanced myxoid liposarcoma (MLPS) patients.
Authors: Chiara Fabbroni, Andrea Franza, Giovanni Fucà, Elena Fumagalli, Alessandro Gronchi, Carlo Morosi, Claudia Sangalli, Paola Collini, Paolo Giovanni Casali, Roberta Sanfilippo
Journal: Journal of Clinical Oncology (2023)

11573 Background: To explore the time to trabectedin failure-free survival after resumption of T in advanced MLPS patients who were stable or responding to T at the time of discontinuation. Methods: We retrospectively collected the cases of all patients with advanced MLPS treated with T at our institution from September 2002, highlighting those who were free from progression (according to RECIST) after 6 cycles of T. Trabectedin failure-free survival (TFFS) was defined as time from the first cycle of T to progression (PD) or death, whichever occurred first. Survival analyses were performed using the Kaplan-Meier method. Results: Since September 2002, 75 patients with recurrent myxoid liposarcoma received T at our institution. A total of 56 patients were free from progression (according to RECIST) after 6 cycles of T and were included in this analysis. Among them, 25/56 (45%) interrupted their treatment in absence of progression, while 31/56 (55%) patients received T until progression of disease. In the former group, 11/25 had surgery of their residual disease, 3/25 received radiotherapy, 5/25 interrupted T for toxicity and 6/25 patients shared the decision to stop with the clinician. Among patients who received surgery, 2/11 had monofocal disease (longest diameter &lt; or = 5cm), 4/11 had monofocal disease (longest diameter between 10-18 cm) and 5/11 had plurifocal disease. The interruption of T in these 25 patients occurred after a median of 12 cycles (interquartile range = 9-14). Median TFFS was 43.4 months (95%CI 38.7-NA). In the concurrent group of patients who received T continuously, the median TFFS was 14.2 months (95% CI: 10.8-21.9). Conclusions: While the longer TFFS of patients undergoing discontinuation cannot be compared with the shorter of those who did not interrupt, the former group being biased favorably (feasibility and exploitation of surgery, other likely determinants of physician’s decision to stop), we speculate that there may be a subgroup of selected patients with advanced myxoid liposarcoma primarily responding to T, who could benefit from a “stop and go” policy, thus prolonging the overall time interval within which T remains active. Prospective studies in selected subgroups of MLPS patients on optimization of treatment strategy with T are worthwhile.
Efficacy and safety analysis of immune checkpoint inhibitors plus angiogenesis inhibitors for treatment of advanced driver-negative NSCLC in elderly patients: A retrospective study.
Authors: Jian Zhang, Hao Wang, Jundong Zhou, Zhonghua Zou, Jie Tan, Jianping Shi, Hui Yang, Jing Xue
Journal: Journal of Clinical Oncology (2023)

e21044 Background: Immune checkpoint inhibitors (ICIs) combined with antiangiogenic drugs may have synergistic effects in elderly patients with advanced driver-gene wild-type non-small cell lung cancer (NSCLC), but its true efficacy remains unclear. In addition, the chemotherapy tolerance of elderly NSCLC patients is poor, and the precise identification of the population who can benefit from ICIs combined with angiogenesis inhibitors is also the focus of current research. Methods: We retrospectively compared the clinical efficacy and safety of ICIs combined with or without antiangiogenic agents in elderly patients with advanced driver-gene negative NSCLC who were ≥65 years old in the Cancer Center of the Affiliated Suzhou Hospital of Nanjing Medical University. The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall survival (OS), objective response rate (ORR), and immune-related adverse events (irAEs). Results: A total of 36 patients in the IA group（Immune checkpoint inhibitors plus angiogenesis inhibitors group) and 43 patients in the NIA group（Immune checkpoint inhibitors without angiogenesis inhibitors group) were enrolled in the study between January 1, 2019 and December 31, 2021. The median follow-up time for patients in IA group and NIA group was 18.2 months (95%CI: 14 - 22.5 months) and 21.4 months (95%CI: 16.7 -26.1 months), respectively. The median PFS and median OS were longer in the IA group compared to the NIA group（8.1 months vs 5.3 months；HR for PFS: 0.778, 95%CI: 0.474-1.276, P = 0.32; NA vs 30.9 months; HR for OS: 0.795, 95%CI: 0.396-1.595, P = 0.519). Subgroup analysis showed that patients in the IA group had significantly longer PFS in the subgroup with PD-L1 expression ≥50% (P = 0.017), and the relationship between treatment regimens and outcomes was still discrepant in different PD-L1 expression levels (P for interaction = 0.002). There was no significant difference in ORR between the two groups (23.3% vs 30.5%, P = 0.465). The incidence of adverse events in IA group was lower than that in NIA group (39.5% vs 19.4%, P = 0.05), and the cumulative incidence of treatment interruptions due to adverse events was significantly reduced (P = 0.045). Conclusions: In elderly patients with advanced driver-gene wild-type NSCLC, the addition of antiangiogenic agents to ICIs therapy did not provide significant clinical benefit, but the incidence of treatment interruptions due to adverse events was significantly reduced. In the subgroup analysis, we found that the clinical benefit of this combination therapy was observed in patients with PD-L1 expression ≥50%, which warrants further exploration. Clinical trial information: NCT05688046 .
PLUME: A single-arm phase II trial evaluating the combination of pembrolizumab and lenvatinib in metastatic uveal melanoma (mUM) patients (pts) previously treated or not with tebentafusp.
Authors: Manuel Rodrigues, Mathilde Saint-Ghislain, Toulsie Ramtohul, Leanne de Koning, Clémentine Bouchez, Elsa Lafite, Zahra Castel Ajgal, Gregoire Marret, Raphaël Sanchez, Pascale Mariani, Sandra Nespoulous, Véronique Gillon, Vincent Servois, Sophie Piperno-Neumann
Journal: Journal of Clinical Oncology (2023)

TPS9613 Background: Up to 50% of pts with uveal melanoma (UM) develop metastases, mainly hepatic, with poor overall survival and limited treatment options as response rate to first-line immune checkpoint inhibitors (ICI) is low in mUM pts. Tebentafusp, a bispecific T-cell engager, was recently approved in this setting but only in HLA A*02-01+ mUM patients. Lenvatinib is a tyrosine kinase inhibitor targeting multiple growth factor receptors including vascular endothelial growth factor receptors (VEGFRs), fibroblast growth factor receptors (FGFRs) and colony-stimulating factor receptor (CSF1-R), which are key pathways in UM. Lenvatinib showed an immune-modulating effect in preclinical models. The combination demonstrated synergic clinical anti-tumor activity in various tumor types including microsatellite-stable endometrial cancers, kidney cancers and ICI-resistant skin melanomas. We hypothesize that combining pembrolizumab with lenvatinib in mUM may lead to an improved immune response in mUM patients. Methods: Fifty-four, ICI-naïve, metastatic UM pts will be enrolled in this monocentric, single-arm phase II trial at Institut Curie, Paris, France. Because previous exposure to tebentafusp might increase the activity of subsequent ICI, the combination will be assessed in two independent cohorts: cohort 1 with HLA A*02-01 neg , tebentafusp-naive patients (22 assessable patients), and cohort 2 with HLA A*02-01 pos pts previously treated with tebentafusp (28 assessable patients). Up to 54 patients may be included according to an 8% drop-out rate. Each participant will receive pembrolizumab (200 mg Q3W, maximum of 35 cycles) plus lenvatinib (starting at 20mg QD) until reaching a discontinuation criterion. Liver MRI and chest-abdomen-pelvis CT will be performed every 9 weeks until progressive disease. Primary objective is to evaluate the progression-free survival (PFS) after nine cycles of treatment (27 weeks) as assessed by the investigator using the RECIST v1.1. Secondary objectives include PFS according to immune RECIST (iRECIST), overall survival, overall response rate, safety and tolerability, quality of life. Inclusion period started mid-July 2022 for two years. To date, twenty-four (21 in cohort 1, 3 in cohort 2) of planned 54 pts have been enrolled in six months. Biospecimens (longitudinal blood samples and tumor tissue at inclusion) will be collected during the study to allow biomarker research. Clinical trial information: NCT05282901 .
Inclusive healthcare for persons with disabilities (PWDs) in advocacy and partnership in breast and cervical cancer screening through the EMPOWER Program.
Authors: Dorothy Ogada Nyongo, Jacqueline Wambua, Catherine Kanari, Eugene Muchai
Journal: Journal of Clinical Oncology (2023)

e22510 Background: With the growing burden of Women cancers in Kenya, integrating cancer screening and prevention to optimize horizontal care delivery models is a paramount approach to strengthening women-centered and cost-effective primary healthcare. EMPOWER is a unique public-private-partnership with the County governments of Kenya, County referral hospitals, County First Ladies Association, International Cancer Institute, Patient organizations (Women4Cancer &amp; Africa cancer Foundation), AMREF and Roche Kenya to demonstrate and deliver integrated cancer prevention, treatment and capacity building including Persons living with Disability (PWDs). Objectives: 1. Generate buy in from county leadership and key stakeholders for PWDs inclusivity in human resources for health. 2. Tangibly demonstrate women PWDs can contribute to community health systems community health volunteers and Promote the Integrated approach screening. 3. Improve access to breast and cervical cancer screening for and through PWDs. Methods: The Project is a multi-faceted advocacy approach, including political leadership engagement and stakeholder alignment. The political leadership engaged with local government officials to raise awareness of the issue and secure support for the initiative. The stakeholder alignment involved working with healthcare providers, community organizations, and PWDs to ensure that the initiative was inclusive and accessible. Qualitative and quantitative methods were used to evaluate the impact of the advocacy efforts. Results: The project was successful in health management teams co-creating selecting and training 50 Women PWDs as community health volunteers, the first in Africa. The advocacy efforts led to an increase in screening rates for PWDs, with 30% more PWDs accessing screening services compared to the previous year. The PWDs involved in the initiative reported high levels of satisfaction with the program and appreciated the opportunity to play an active role in their own healthcare. Conclusions: The project demonstrated that it is possible to effectively implement inclusive healthcare for persons with disabilities (PWDs) through advocacy and partnerships. The successful adoption of advocacy to address disparities in breast and cervical cancer screening among PWDs highlights the potential for scaling up this work to reach a larger population. The alignment of political leadership and stakeholders, highlights the crucial role of creating a supportive environment to ensure the rights of PWDs to the highest attainable standard of health are upheld. Future efforts to address health disparities among PWDs should build on this approach, leveraging advocacy, partnerships, and cocreation of implementation to drive change at the community level.
Genomic landscape of cancer of unknown primary site (CUP): Mayo Clinic experience.
Authors: Mayra Duran, Riham Suleiman, Sandra Algarin Perneth, Ricardo Loor Torres, Cristian Soto Jacome, Jennifer Gile, Rondell P. Graham, Stephan Thome, Jose Caetano Villasboas, Roberto Antonio Leon-Ferre, Thorvardur Ragnar Halfdanarson, Harry E Fuentes Bayne
Journal: Journal of Clinical Oncology (2023)

e18807 Background: CUP represents both a diagnostic and a management challenge. Despite improvements through sophisticated imaging modalities, specific and sensitive testing using immunohistochemistry, a concrete determination of the site of origin of the primary tumor can still be a diagnostic challenge Hereby, we described the genomic landscape of patients with CUP treated at our institution. Methods: Retrospective study of patients with CUP treated at Mayo Clinic Rochester MN from 2010 to 2021. Next generation sequencing (NGS) information was abstracted, and alterations were ranked into different levels of actionability following the Onco KB framework. All data were analyzed by the SPSS version 22.0 software (SPSS, Chicago, IL, United States). Results: From a total of 214 patients, we identified 67 (32%) patients in whom NGS was performed. Among patients with available NGS the median age was 64 years (range: 35-86) and 51% were female. the most prevalent histology included adenocarcinoma (39%), carcinoma NOS (31%), and neuroendocrine tumors (12%). NGS on tumor (t-NGS) was available in 56 (84 %) patients, circulating tumor NGS (b-NGS) was available in 12 (18%) patients, and only 1 patient had both testing available. Among the 56 patients with available t-NGS, MSI-high was detected in 9 patients, whereas among the 12 patients with available b-NGS, MSI-high was detected in 8 patients; yielding an MSI-high detection rate of 16% and 67% for t-NGS and b-NGS. In this cohort, there were a total of 474 genomic alterations detected from which 103 (22 %) were able to be ranked into one therapeutic level following the OncoKB framework. Genomic alterations were most observed among patients with carcinoma (n = 50, 48.53%) adenocarcinoma (n = 33, 32.03 %), squamous cell carcinoma (n = 3, 2.91 %) and neuroendocrine tumor (n = 2, 1.94%). Following the OncoKB framework, 39-level 1 genomic alterations were detected in a total of 14 genes. The most common level 1 genomic alterations comprised the BRCA2 (20.51%), NF1 ATM (17.95%) and HER2/NEU (ERBB2) (15.38%) genes. Therapeutic level 2 included 51 genomic alterations in 13 genes of which KRAS (17.65%), BRAF (15.69%), and BRCA2 (15.69%) were the most prevalent mutated genes. Additionally, level R comprised 13 genomic alterations in the following genes: KRAS (69.23) NRAS (23.08%) and PDGFRA (7.69%). Conclusions: CUP are malignancies rich in potentially actionable alterations, and NGS of tissue and blood samples can inform systemic therapy decisions. Alteration-specific targeted therapy may be an option for a substantial proportion of patients. NGS of tumor tissue or blood should be considered for all patients with CUP.